Successful Pregnancy in a Woman of Advanced Maternal Age at Sixteen Months Post-Roux-en-Y Gastric Bypass Revision

Obesity, defined as body mass index (BMI) > 30 kg/m2, complicates maternal and neonatal outcomes. Bariatric surgery (BS) is an option for weight reduction in several populations, including reproductive-aged women. However, there is a lack of consensus regarding the ideal time interval between BS and pregnancy. We report the case of a 43-year-old Hispanic female who underwent an initial Roux-en-Y gastric bypass (RYGB) in 2011, followed by a revision eight years later in 2019. The revision entailed the reduction of the gastric pouch size and the excision of the remnant stomach. It occurred sixteen months before the conception of her second pregnancy. Despite advanced maternal age and nutritional challenges following BS, this patient delivered a healthy male neonate and maintained a net weight loss compared to her preoperative weight. Factors leading to this positive outcome included the patient's adherence to dietary recommendations following the procedure and using weight loss adjuncts (phentermine and topiramate) to promote post-procedure weight loss. Sixteen months between RYGB revision and conception can lead to positive pregnancy outcomes, even in women of advanced maternal age and multiple prior BS. Further studies are required to understand better the optimal interval to reduce maternal and neonatal complications following RYGB specifically and the use of medications as weight loss adjuncts.


Introduction
Approximately 62.5% of adults in the Americas are overweight or obese [1]. In the USA, candidates for bariatric surgery (BS) must have a body mass index (BMI) ≥35 kg/m 2 (regardless of presence, absence, or severity of co-morbidities) or a BMI ≥30 kg/m 2 with type 2 diabetes, or a BMI of 30-34.9 kg/m 2 and unable to achieve sustainable weight loss or co-morbidity improvement via nonsurgical methods [2]. Options for BS include procedures that restrict stomach size (laparoscopic sleeve gastrectomy [LSG]), limit nutrient absorption (biliopancreatic diversion), or both (Roux-en-Y gastric bypass [RYGB]). Biliopancreatic diversion with duodenal switch is a procedure that involves both food restriction and decreased absorption, similar to RYGB. Compared to laparoscopic RYGB, LSG is a simpler procedure as it does not require a gastrointestinal anastomosis or intestinal bypass [3]. Between 1998 -2005, 83% of BS procedures in the United States were performed on women of reproductive age (18-45 years old) [4].
Obesity is detrimental to fertility because it interferes with normal ovarian and endometrial physiology [5]. It can also increase the risk of gestational diabetes mellitus, preeclampsia, cesarean delivery, and infectious morbidity [6]. While one can understand why women with obesity may choose to undergo BS before conception, the procedure alone is not a treatment for infertility [5]. BS can lead to severe nutritional deficiencies if patients do not adhere to the appropriate diet postoperatively [6].
We report the case of a pregnancy in a woman of advanced maternal age that resulted in positive outcomes despite an interval of only sixteen months between RYGB revision and conception.
A draft of this article was previously posted to the Research Square preprint platform on September 28, 2022.

Case Presentation
We present the case of a 43-year-old Hispanic female who was G2P2A0 and eight years status post an RYGB procedure. Sixteen months before conception, she underwent an RYGB revision in 2019 to treat morbid obesity due to weight recurrence. The revision entailed the reduction of the gastric pouch to approximately four centimeters in length and the narrowing of the pouch through the angle of His
Given the growing prevalence of obesity in females ages 20-39, weight reduction has become an increasingly important aspect of preconception counseling [9]. Excess adipose tissue evolves into an active endocrine organ with harmful systemic effects, including insulin resistance and defective placental development [10].
Complications associated with maternal obesity during pregnancy include gestational hypertension, preeclampsia, gestational diabetes, preterm birth, and large infants for their gestational age [11]. The Barker hypothesis postulates that maternal obesity increases the propensity for adult cardiovascular disease among infants due to changes in metabolic programming in utero [12]. Thus, BS may be a suitable treatment for pre-pregnancy obesity in women who meet the established criteria.
While the American Society for Metabolic and Bariatric Surgery recommends 12-18 months after surgery and before pregnancy, there is no consensus regarding this time interval in the literature [13,14]. Furthermore, this recommendation is not specific to the type of BS performed, the involvement of any revisions to the index surgery, or the consideration of variables about the mother. Rapid weight loss can lead to higher fertility rates by improving menstrual regularity and relieving the symptoms of the polycystic ovarian syndrome [15]. However, the dramatic weight loss following BS can hinder follicle development [16]. Studies revealed that pregnancy <12 months following RYGB was associated with a higher incidence of urinary tract infection, inadequate birth weight, and dumping syndrome compared to pregnancies initiated 12-24 months after the procedure [17]. More research will be required to understand the full impact of the length of this interval on pregnancy outcomes.
This case is unique because of our patient's advanced maternal age (43 years old) and history of two BS procedures. Fecundity begins to decline at age 32 and further declines after age 37 due to a decrease in egg quality and circulating hormone levels [18]. While we did not have access to her obstetrical records, our patient reported no difficulties with conception. Studies report that neonates born to mothers who had undergone RYGB surgery were likelier to have lower fetal growth rates [13]. Although our patient had undergone two BS procedures, she did not experience this complication. More research will be needed to understand the potential detrimental physiological and nutritional changes and their impact on pregnancies among women who have undergone BS.
Due to the start of the coronavirus-19 pandemic in March 2020, her appointment was a telehealth appointment, and this patient was lost to follow-up. Her first in-person appointment with the bariatric surgery clinic following the birth of her child was in June 2021.
The patient was treated with phentermine starting three months postoperatively; topiramate was added fifteen months postoperatively due to inadequate weight loss. The use of phentermine and topiramate as weight-loss adjuncts was approved by the United States Food and Drug Administration in 2012 [19]. Studies show increased efficacy of these weight loss medications when combined with laparoscopic sleeve gastrectomy versus RYGB. These drugs resulted in a 2.8% versus a 0.3% total body weight loss [20]. More data will be needed to understand the appropriate use of the adjuncts, particularly in reproductive-aged women.
Patients who have undergone BS should be followed up every three months for two years to screen for nutritional deficiencies [16]. Deficiencies in vitamins A, B12, K, iron, folate, and calcium can harm the mother's and growing fetus's health. After the onset of the COVID-19 pandemic in March 2020, our patient was followed by telemedicine appointments for one year. The electronic health records documenting these encounters do not indicate any desire to conceive, although our patient's obstetrician was aware. While there are currently no specific guidelines, our patient presented at advanced maternal age and thus may have benefitted from counseling regarding pregnancy after BS.

Conclusions
While the American Society for Metabolic and Bariatric Surgery recommends 12-18 months after surgery and prior to pregnancy, there is no consensus regarding this time interval in the literature. This case is valuable because it illustrates that a healthy pregnancy following RYGB revision is possible, even in a female of advanced maternal age with sixteen months between the procedure and conception. Furthermore, this patient sustained a net weight loss, specifically with phentermine and topiramate. Further studies are required to understand better the optimal interval to reduce maternal and neonatal complications following RYGB specifically and the use of medications as weight loss adjuncts.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.